Abstract

A considerable proportion of lung adenocarcinoma (LADC) cases develop through activation of oncogenes, i.e., somatic mutations in either the EGFR (10–40%) or KRAS (10–20%) genes, or fusion of the ALK gene (5%) with the EML4 or KIF5B genes, in a mutually exclusive manner. Tyrosine kinase inhibitors that target EGFR and ALK proteins are particularly effective for treating LADCs carrying EGFR mutations and ALK fusions, respectively. In this study, whole transcriptome sequencing (RNA sequencing) of 30 Japanese LADCs and three adjacent non-cancerous lung tissues was performed to identify novel chimeric fusion transcripts that could be potential targets for therapy. Analysis of more than 2 × 107 paired-end reads obtained by RNA sequencing and subsequent validation by Sanger sequencing of the reverse transcription (RT)-PCR products identified EML4-ALK fusions in two cases and a few other gene fusions in each single case. The two EML4-ALK positive LADC cases were negative for EGFR and KRAS mutations and also negative for other gene fusions. Therefore, the authenticity of ALK fusions as a driver mutation was validated. The prevalence and oncogenic property of novel gene fusions identified are being studied.